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Abstract:

Infantile hemangiomas are the most common benign tumors of infancy, characterized by unregulated angiogenesis and endothelial cells with high mitotic rate. Although spontaneous regression occurs, sometimes treatment is required and alternatives to corticosteroids should be considered to reduce side effects. Imiquimod is an imidazoquinoline, approved for some skin pathologies other than hemangioma. It is proposed that the effectiveness of imiquimod comes from the activation of immune cells at tumor microenvironment. However, the possibility to selectively kill different cell types and to directly impede angiogenesis has been scarcely explored in vitro for endothelial cells. In this work we showed a dramatic cytotoxicity on hemangioma cell, with a significant lower IC50 value in hemangioma compared to normal endothelial cells and melanoma (employed as a non-endothelial tumor cell line). Nuclear morphometric and flow-cytometry assays revealed imiquimod-induced apoptosis on hemangioma and melanoma cells but a small percentage of senescence on normal endothelial cells. At sub-lethal conditions, cell migration, a key step in angiogenesis turned out to be inhibited in a tumor-selective manner along with actin cytoskeleton disorganization on hemangioma cells. Altogether, these findings pointed out the selective cytotoxic effects of imiquimod on transformed endothelial cells, evidencing the potential for imiquimod to be a therapeutic alternative to reduce extensive superficial hemangioma lesions. © 2018 Elsevier B.V.

Registro:

Documento: Artículo
Título:Selective hemangioma cell dysfunction and apoptosis triggered by in vitro treatment with imiquimod
Autor:Rocco, R.; Alegre, N.; Pozner, R.; Wainstok, R.; Gazzaniga, S.
Filiación:Laboratorio de Biología Tumoral, Dpto. de Química Biológica IQUIBICEN-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Institute of Experimental Medicine (IMEX) -CONICET, National Academy of Medicine, Buenos Aires, Argentina
Palabras clave:Cytotoxicity; Endothelium; Hemangioma; Imiquimod; imiquimod; aminoquinoline derivative; antineoplastic agent; imiquimod; actin filament; angiogenesis; animal cell; apoptosis; Article; capillary hemangioma; cell migration; cell transformation; controlled study; drug cytotoxicity; drug selectivity; endothelium cell; flow cytometry; hemangioma cell; IC50; immunocompetent cell; immunostimulation; in vitro study; melanoma cell line; morphometry; mouse; nonhuman; priority journal; stress fiber; tumor cell; tumor microenvironment; animal; apoptosis; cell aging; cell motion; cell nucleus; cell survival; cytoskeleton; drug effects; experimental melanoma; hemangioma; human; pathology; skin tumor; tumor cell line; ultrastructure; Aminoquinolines; Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Survival; Cellular Senescence; Cytoskeleton; Endothelial Cells; Hemangioma; Humans; Melanoma, Experimental; Mice; Skin Neoplasms; Stress Fibers
Año:2018
Volumen:288
Página de inicio:82
Página de fin:88
DOI: http://dx.doi.org/10.1016/j.toxlet.2018.01.016
Título revista:Toxicology Letters
Título revista abreviado:Toxicol. Lett.
ISSN:03784274
CODEN:TOLED
CAS:imiquimod, 99011-02-6; Aminoquinolines; Antineoplastic Agents; imiquimod
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03784274_v288_n_p82_Rocco

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Citas:

---------- APA ----------
Rocco, R., Alegre, N., Pozner, R., Wainstok, R. & Gazzaniga, S. (2018) . Selective hemangioma cell dysfunction and apoptosis triggered by in vitro treatment with imiquimod. Toxicology Letters, 288, 82-88.
http://dx.doi.org/10.1016/j.toxlet.2018.01.016
---------- CHICAGO ----------
Rocco, R., Alegre, N., Pozner, R., Wainstok, R., Gazzaniga, S. "Selective hemangioma cell dysfunction and apoptosis triggered by in vitro treatment with imiquimod" . Toxicology Letters 288 (2018) : 82-88.
http://dx.doi.org/10.1016/j.toxlet.2018.01.016
---------- MLA ----------
Rocco, R., Alegre, N., Pozner, R., Wainstok, R., Gazzaniga, S. "Selective hemangioma cell dysfunction and apoptosis triggered by in vitro treatment with imiquimod" . Toxicology Letters, vol. 288, 2018, pp. 82-88.
http://dx.doi.org/10.1016/j.toxlet.2018.01.016
---------- VANCOUVER ----------
Rocco, R., Alegre, N., Pozner, R., Wainstok, R., Gazzaniga, S. Selective hemangioma cell dysfunction and apoptosis triggered by in vitro treatment with imiquimod. Toxicol. Lett. 2018;288:82-88.
http://dx.doi.org/10.1016/j.toxlet.2018.01.016